Sodium Carbonate → 5-(3-Bromo-4-ethyl-anilino)-8-[(6-methoxy-pyridin-3-yl)-methyl]-[1,6]naphthyridine

HRID 2252850Notes

Reaction equation

HRID 2252850 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]([CH2:12][C:13]2[CH:14]=[N:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=2)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.[Br:21][C:22]1[CH:23]=[C:24]([CH:26]=[CH:27][C:28]=1[CH2:29][CH3:30])[NH2:25].Cl.O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+]>CO.CCOC(C)=O>[Br:21][C:22]1[CH:23]=[C:24]([CH:26]=[CH:27][C:28]=1[CH2:29][CH3:30])[NH:25][C:2]1[N:11]=[CH:10][C:9]([CH2:12][C:13]2[CH:14]=[N:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=2)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.[Br:21][C:22]1[CH:23]=[C:24]([CH:26]=[CH:27][C:28]=1[CH2:29][CH3:30])[NH:25][C:2]1[N:11]=[CH:10][C:9]([CH2:12][C:13]2[CH:14]=[N:15][C:16]([OH:19])=[CH:17][CH:18]=2)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 204431481,4-Dioxane hydrochlorideHCID 206364295-Chloro-8-[(6-methoxy-pyridin-3-yl)-methyl]-[1,6]naphthyridineHCID 223456173-Bromo-4-ethylaniline

Product 2

HCID 206364225-(3-Bromo-4-ethyl-anilino)-8-[(6-methoxy-pyridin-3-yl)-methyl]-[1,6]naphthyridineHCID 178436567HCID 178436567, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Under a N2 atmosphere, 241 mg (0.84 mmol) of 5-chloro-8-[(6-methoxy-pyridin-3-yl)-methyl]-[1,6]naphthyridine in 4 ml of methanol are mixed with 252 mg (1.26 mmol) of 3-bromo-4-ethyl-aniline (Ex. 9) and 0.21 ml of 4 N HCl/dioxane and stirred for 16 h at 80° C. The cooled reaction mixture is taken up with diluted Na2CO3 solution and EtOAc. The water phase is separated and extracted twice with EtOAc. The organic phases are dried (Na2SO4) and concentrated by evaporation. Column chromatography (SiO2, toluene/EtOAc 2:1→EtOAc/acetone/EtOH 4:4:1→acetone/EtOH 9:1) and crystallisation from hexane yield 5-(3-bromo-4-ethyl-anilino)-8-[(6-methoxy-pyridin-3-yl)-methyl]-[1,6]naphthyridine 37a (m.p. 142-146° C.; FAB-MS: (M+H)+=449/451; HPLC(gradient20-100) tRef=10.9) and 5-(3-bromo-4-ethyl-anilino)-8-[(6-hydroxy-pyridin-3-yl)-methyl]-[1,6]naphthyridine 37b (m.p. 262-265° C.; FAB-MS: (M+H)+=435/437; HPLC(gradient20-100) tRef=9.3).

Workup

  1. customThe cooled reaction mixture
  2. customThe water phase is separated
  3. extractionextracted twice with EtOAc
  4. dry with materialThe organic phases are dried (Na2SO4)
  5. concentrationconcentrated by evaporation
  6. customColumn chromatography (SiO2, toluene/EtOAc 2:1→EtOAc/acetone/EtOH 4:4:1→acetone/EtOH 9:1) and crystallisation from hexane

Sources & evidence

ORD record
ord-e9477dd85b664a5f972074cb70fea679
Source dataset
uspto-grants-2008_01
Patent number
US07323474B2

Reaction notes

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